tbuckley/cabot-search huggingface dataset:
Underwater endoscopic mucosal resection after endoscopic ultrasound examination for safe and reliable complete resection of a deeply invasive submucosal cecal cancer
Authors: Kazuaki Akahoshi, Takaaki Morikawa, Hisashi Fukuda, Yoshikazu Hayashi, Kozue Ando, Alan Kawarai Lefor, Hironori Yamamoto
Journal: Endoscopy (2022)

The risk of lymph node metastases from invasive submucosal (T1b) colorectal cancers > 1000 µm deep is 1.3 % according to the Japanese guideline [1]. Over 98 % of stage T1b cancers without evidence of lymphovascular invasion, poor differentiation, or budding have no associated lymph node metastases. Achieving an endoscopic R0 resection allows curative resection of the majority of stage T1b cancers. Although magnifying colonoscopy can diagnose stage T1b cancers, pathological evaluation using specimens from an R0 resection is more reliable. If a cancer is diminutive and possibly a stage T1b cancer, total excision for pathological evaluation may avoid surgical resection but, to be justified, must be safe and reasonable. Although endoscopic submucosal dissection is reliable for R0 resection, Fukuda et al. recently showed that underwater endoscopic mucosal resection (UEMR) can completely resect stage T1b lesions [2]. Endoscopic ultrasound (EUS) demonstrates the submucosa under the tumor, which facilitates decision-making about UEMR.
Deconvolution of malignant pleural effusions immune landscape unravels a novel macrophage signature associated with worse clinical outcome in lung adenocarcinoma patients
Authors: Sara Bruschini, Matteo Pallocca, Eleonora Sperandio, Lorenzo D’Ambrosio, Francesca Ascenzi, Claudia De Vitis, Valentina Salvati, Antonella Esposito, Simona Di Martino, Francesca De Nicola, Francesca Paolini, Luigi Fattore, Gabriele Alessandrini, Francesco Facciolo, Maria Laura Foddai, Massimiliano Bassi, Federico Venuta, Michela D’Ascanio, Alberto Ricci, Antonio D’ Andrilli, Christian Napoli, Luigi Aurisicchio, Maurizio Fanciulli, Erino Angelo Rendina, Gennaro Ciliberto, Rita Mancini
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Immune checkpoint inhibitors are still unable to provide clinical benefit to the large majority of non-small cell lung cancer (NSCLC) patients. A deeper characterization of the tumor immune microenvironment (TIME) is expected to shed light on the mechanisms of cancer immune evasion and resistance to immunotherapy. Here, we exploited malignant pleural effusions (MPEs) from lung adenocarcinoma (LUAD) patients as a model system to decipher TIME in metastatic NSCLC. Methods Mononuclear cells from MPEs (PEMC) and peripheral blood (PBMC), cell free pleural fluid and/or plasma were collected from a total of 24 LUAD patients and 12 healthy donors. Bulk-RNA sequencing was performed on total RNA extracted from PEMC and matched PBMC. The DEseq2 Bioconductor package was used to perform differential expression analysis and CIBERSORTx for the regression-based immune deconvolution of bulk gene expression data. Cytokinome analysis of cell-free pleural fluid and plasma samples was performed using a 48-Plex Assay panel. THP-1 monocytic cells were used to assess macrophage polarization. Survival analyses on NSCLC patients were performed using KM Plotter (LUAD, N=672; lung squamous cell carcinoma, N=271). Results Transcriptomic analysis of immune cells and cytokinome analysis of soluble factors in the pleural fluid depicted MPEs as a metastatic niche in which all the components required for an effective antitumor response are present, but conscripted in a wound-healing, proinflammatory and tumor-supportive mode. The bioinformatic deconvolution analysis revealed an immune landscape dominated by myeloid subsets with the prevalence of monocytes, protumoral macrophages and activated mast cells. Focusing on macrophages we identified an MPEs-distinctive signature associated with worse clinical outcome in LUAD patients. Conclusions Our study reports for the first time a wide characterization of MPEs LUAD microenvironment, highlighting the importance of specific components of the myeloid compartment and opens new perspectives for the rational design of new therapies for metastatic NSCLC.
TNF blockade enhances the efficacy of myxoma virus-based oncolytic virotherapy
Authors: Miriam Valenzuela-Cardenas, Cody Gowan, Parker Dryja, Mee Y Bartee, Eric Bartee
Journal: Journal for ImmunoTherapy of Cancer (2022)

Oncolytic virotherapy (OV) represents a method to treat a variety of solid tumors by inducing antitumor immune responses. While this therapy has been extremely efficacious in preclinical models, translating these successes into human patients has proven challenging. One of the major reasons for these failures is the existence of immune-regulatory mechanisms, which dampen the efficacy of virally induced antitumor immunity. Unfortunately, the full extent of these immune-regulatory pathways remains unclear.
Unbiased antimicrobial resistance prevalence estimates through population-based surveillance
Authors: Frank van Leth, Constance Schultsz
Journal: Clinical Microbiology and Infection (2022)

Current antimicrobial resistance surveillance (AMR) is mainly laboratory based. This approach can have inherent biases given the potential for selective specimen submission for microbiological analysis and for its inability to map antibiotic susceptibility test results to a clinical syndrome.To discuss the need for population-based surveillance of AMR, and highlight the pros and cons of threshold surveys.Studies on methodology for AMR surveillance published in the last 10 years, obtained through a PubMed search on antimicrobial resistance (all fields) and surveillance/method (MeSH term).We discuss the use of threshold surveys to overcome the challenge of sample size in population-bases AMR surveys, which are a suitable approach in both low- and high-resource settings.Scale up in the use of population-based threshold survey on the prevalence of AMR will provide necessary information to triangulate the data from routinely-reported laboratory-based AMR surveillance at the local, national, and global level.
Successful treatment of hemorrhagic radiation esophagitis with radiofrequency ablation
Authors: Flavius-Stefan Marin, Rachel Hallit, Romain Coriat, Stanislas Chaussade, Frédéric Prat, Maximilien Barret
Journal: Endoscopy (2022)

A 78-year-old man, with a history of T2N0M0 esophageal adenocarcinoma treated with chemoradiotherapy 2 years before, was referred to our department with recurrent upper gastrointestinal bleeding (hemoglobin level of 8.8 g/dl), attributed to radiation esophagitis. He had been admitted three times before for red blood cell transfusion and endoscopic treatment with argon plasma coagulation. Initial esophagogastroduodenoscopy showed diffuse telangiectasias of the lower esophagus and gastroesophageal junction with signs of recent bleeding ([Fig. 1 a]). Radiofrequency ablation (RFA) of the lower esophagus and gastroesophageal junction was performed using a double 10 J/cm2 ablation with a 360° Express balloon catheter (Medtronic, Minneapolis, Minnesota, USA) ([Video 1], [Fig.1 b]), followed by double-dose proton pump inhibitors. Despite no recurrent digestive bleeding, persistent iron deficiency anemia prompted repeat esophagogastroduodenoscopies, including two RFA treatment sessions every 6 months, using a triple 12 J/cm² RFA application with a focal Halo 90 catheter. The 15-month follow-up esophagogastroduodenoscopy showed a significant regression of the esophageal telangiectasias ([Fig. 1 c]). No recurrent bleeding occurred and hemoglobin level remained stable.
The Molecular Landscape of Pancreatobiliary Cancers for Novel Targeted Therapies From Real-World Genomic Profiling
Authors: Kumiko Umemoto, Hiroyuki Yamamoto, Ritsuko Oikawa, Hiroyuki Takeda, Ayako Doi, Yoshiki Horie, Hiroyuki Arai, Takashi Ogura, Takuro Mizukami, Naoki Izawa, Jay A Moore, Ethan S Sokol, Yu Sunakawa
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract Background Chemotherapies have limited efficacy in pancreatic cancer (PC) and biliary tract cancer (BTC), underscoring the need for new regimens. Recently, tumor-agnostic approaches have been developed for some targeted therapies in advanced solid tumors; however, the frequency of alterations by clinical and genomic background is unclear in PC and BTC. Methods To assess the frequencies of druggable gene alterations and investigate new potential therapeutic targetable genomic alterations, advanced PC and BTC patients were tested with comprehensive genomic profiling at Foundation Medicine during the course of clinical care. Results A total of 16 913 PC patients and 3031 BTC patients were available for analyses, and frequencies of genomic alterations were stratified by age (≥40 years or &amp;lt;40 years), microsatellite instability status, tumor mutational burden status (high ≥10 or low &amp;lt;10 Muts/Mb), and select genomic alterations. Alterations in BRCA2, BRAF, ERBB2, CDK12, PIK3CA, FGFR2, EGFR, and other potential targets were seen across cohorts, with enrichment observed within particular subsets such as in PC patients lacking a KRAS mutation. In BTC patients, the rate of ERBB2 amplification was statistically significantly higher in the tumor mutational burden–high population (23.3% vs 13.7%). Interestingly, CDK12 rearrangement was observed in BTC patients with ERBB2 amplification tumors. In patients younger than 40 years, FGFR2 rearrangement (4%) was observed in PC: GATA6 amplification (11.1%) and rearrangement of BRAF (2.8%)FGFR2 (5.6%) was observed in BTC patients. Conclusions We identified an appreciable frequency of immunotherapy biomarkers and targetable gene alterations in both PC and BTC, with notable frequencies in PC samples lacking KRAS mutations and children or adolescent and young adult populations, that should encourage comprehensive genomic profiling testing.
Abstract A023: Progression and regression dynamics of bivalve transmissible neoplasia in the soft-shell clam (<i>Mya arenaria</i>) after both natural and experimental exposure
Authors: Rachael M. Giersch, Marisa A. Yonemitsu, Samuel F.M. Hart, Michael J. Metzger
Journal: Cancer Research (2022)

Abstract This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Proffered Abstracts section (PR017) of the Conference Proceedings. Citation Format: Rachael M. Giersch, Marisa A. Yonemitsu, Samuel F.M. Hart, Michael J. Metzger. Progression and regression dynamics of bivalve transmissible neoplasia in the soft-shell clam (Mya arenaria) after both natural and experimental exposure [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A023.
Resistance mutations in SARS-CoV-2 omicron variant in patients treated with sotrovimab
Authors: Camille Vellas, Pauline Trémeaux, Arnaud Del Bello, Justine Latour, Nicolas Jeanne, Noémie Ranger, Chloé Danet, Guillaume Martin-Blondel, Pierre Delobel, Nassim Kamar, Jacques Izopet
Journal: Clinical Microbiology and Infection (2022)
Acid‐Responsive Nanoporphyrin Evolution for Near‐Infrared Fluorescence‐Guided Photo‐Ablation of Biofilm
Authors: Mengyao Yang, Zulal Özdemir, Heejeong Kim, Sanghee Nah, Erik Andris, Xingshu Li, Zdeněk Wimmer, Juyoung Yoon
Journal: Advanced Healthcare Materials (2022)

Abstract Combating biofilm infections remains a challenge due to the shield and acidic conditions. Herein, an acid‐responsive nanoporphyrin (PN3‐NP) based on the self‐assembly of a water‐soluble porphyrin derivative (PN3) is constructed. Additional kinetic control sites formed by the conjugation of the spermine molecules to a porphyrin macrocycle make PN3 self‐assemble into stable nanoparticles (PN3‐NP) in the physiological environment. Noteworthily, near‐infrared (NIR) fluorescence monitoring and synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) effects of PN3‐NP can be triggered by the acidity in biofilms, accompanied by intelligent transformation into dot‐like nanospheres. Thus, damage to normal tissue is effectively avoided and accurate diagnosis and treatment of biofilms is achieved successfully. The good results of fluorescence imaging‐guided photo‐ablation of antibiotic‐resistant strains methicillin‐resistant Staphylococcus aureus (MRSA) biofilms verify that PN3‐NP is a promising alternative to antibiotics. Meanwhile, this strategy also opens new horizons to engineer smart nano‐photosensitizer for accurate diagnosis and treatment of biofilms.
Empirical Evaluations of Clinical Trial Designs
Authors: Lorenzo Trippa, Sergio Bacallado
Journal: JAMA Network Open (2022)

Kristine Broglio, MS; William J. Meurer, MD, MS; Valerie Durkalski, PhD; Qi Pauls, MS; Jason Connor, PhD; Donald Berry, PhD; Roger J. Lewis, MD, PhD; Karen C. Johnston, MD, MS; William G. Barsan, MD
Re: Longbin Xiong, Jane K. Nguyen, Yulu Peng, et al. What Happens to the Preserved Renal Parenchyma After Clamped Partial Nephrectomy? Eur Urol. 2022;81:492–500. https://doi.org/10.1016/j.eururo.2021.12.036
Authors: Shangqing Ren, Shan Zhong, Shida Fan, Xinglan Li, Fang Zhou, Dong Wang
Journal: European Urology (2022)
Evaluation of the Relationship Between Serum Urate Levels, Clinical Manifestations of Gout, and Death From Cardiovascular Causes in Patients Receiving Febuxostat or Allopurinol in an Outcomes Trial
Authors: Kenneth G. Saag, Michael A. Becker, William B. White, Andrew Whelton, Jeffrey S. Borer, Philip B. Gorelick, Barbara Hunt, Majin Castillo, Lhanoo Gunawardhana
Journal: Arthritis & Rheumatology (2022)

To investigate whether serum urate levels, number of gout flares, and tophi burden are related to death from cardiovascular (CV) causes after treatment with febuxostat or allopurinol in patients with gout from the Cardiovascular Safety of Febuxostat or Allopurinol in Patients With Gout and Cardiovascular Comorbidities (CARES) trial.Patients were randomly assigned to receive febuxostat (40 mg or 80 mg once daily, according to serum urate levels at week 2) or allopurinol titrated in 100-mg increments from 200-400 mg or 300-600 mg (with dose determined according to kidney function). Changes from baseline in serum urate level, gout flares, and tophus resolution were key exploratory efficacy parameters in the overall population and in subgroups of patients who died and those who did not die from a CV-related cause. The latter subgroup included patients who died due to non-CV causes and those who did not die due to any cause.Patients received treatment with febuxostat (n = 3,098) or allopurinol (n = 3,092) for a median follow-up period of 32 months (for a maximum of 85 months). In the overall population, mean serum urate levels were lower in those receiving febuxostat compared with those receiving allopurinol at most study visits. There were no associations between serum urate levels and death from CV causes with febuxostat. The number of gout flares requiring treatment was higher within 1 year of treatment with febuxostat compared with allopurinol (mean incidence of gout flares per patient-years of exposure 1.33 versus 1.20), but was comparable thereafter and decreased overall throughout the study period (mean incidence of gout flares per patient-years of exposure 0.35 versus 0.34 after 1 year of treatment; overall mean incidence 0.68 versus 0.63) irrespective of whether the patient died from a CV-related cause. Overall, 20.8% of patients had ≥1 tophus at baseline; tophus resolution rates were similar between treatment groups, with cumulative resolution rates of >50%.In the CARES trial, febuxostat and allopurinol (≤600 mg doses) had comparable efficacy in patients with gout and CV disease, and there was no evidence of a relationship between death from CV causes and serum urate levels, number of gout flares, or tophus resolution among the patients receiving febuxostat.
Role of adipose tissue macrophages in obesity-related disorders
Authors: Svetoslav Chakarov, Camille Blériot, Florent Ginhoux
Journal: The Journal of Experimental Medicine (2022)

The obesity epidemic has led researchers and clinicians to reconsider the etiology of this disease and precisely decipher its molecular mechanisms. The excessive accumulation of fat by cells, most notably adipocytes, which play a key role in this process, has many repercussions in tissue physiology. Herein, we focus on how macrophages, immune cells well known for their tissue gatekeeping functions, assume fundamental, yet ill-defined, roles in the genesis and development of obesity-related metabolic disorders. We first discuss the determinants of the biology of these cells before introducing the specifics of the adipose tissue environment, while highlighting its heterogeneity. Finally, we detail how obesity transforms both adipose tissue and local macrophage populations. Understanding macrophage diversity and their cross talk with the diverse cell types constituting the adipose tissue environment will allow us to frame the therapeutic potential of adipose tissue macrophages in obesity.
Correction: Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations
Authors: Federico Rodriguez-Porcel, Kathryn A. Wyman-Chick, Carla Abdelnour Ruiz, Jon B. Toledo, Daniel Ferreira, Prabitha Urwyler, Rimona S. Weil, Joseph Kane, Andrea Pilotto, Arvid Rongve, Bradley Boeve, John-Paul Taylor, Ian McKeith, Dag Aarsland, Simon J. G. Lewis
Journal: Translational Neurodegeneration (2022)
Dichotomous role of miR193b-3p in diabetic foot ulcers maintains inhibition of healing and suppression of tumor formation
Authors: Jelena Marjanovic, Horacio A. Ramirez, Ivan Jozic, Rivka C. Stone, Tongyu C. Wikramanayake, Cheyanne R. Head, Beatriz Abdo Abujamra, Nkemcho Ojeh, Robert S. Kirsner, Hadar Lev-Tov, Irena Pastar, Marjana Tomic-Canic
Journal: Science Translational Medicine (2022)

Despite the hyperproliferative environment marked by activation of β-catenin and overexpression of c-myc, the epidermis surrounding chronic diabetic foot ulcers (DFUs) is clinically hypertrophic and nonmigratory yet does not undergo malignant transformation. We identified miR193b-3p as a master regulator that contributes to this unique cellular phenotype. We determined that induction of tumor suppressor miR193b-3p is a unique feature of DFUs that is not found in venous leg ulcers, acute wounds, or cutaneous squamous cell carcinoma (SCC). Genomic analyses of DFUs identified suppression of the miR193b-3p target gene network that orchestrates cell motility. Inhibition of migration and wound closure was further confirmed by overexpression of miR193b-3p in human organotypic and murine in vivo wound models, whereas miR193b-3p knockdown accelerated wound reepithelialization in human ex vivo and diabetic murine wounds in vivo. The dominant negative effect of miR193b-3p on keratinocyte migration was maintained in the presence of promigratory miR31-5p and miR15b-5p, which were also overexpressed in DFUs. miR193b-3p mediated antimigratory activity by disrupting stress fiber formation and by decreasing activity of GTPase RhoA. Conversely, miR193b-3p targets that typically participate in malignant transformation were found to be differentially regulated between DFUs and SCC, including the proto-oncogenes KRAS (Kirsten rat sarcoma viral proto-oncogene) and KIT (KIT proto-oncogene). Although miR193b-3p acts as a tumor suppressor contributing to low tumor incidence in DFUs, it also acts as a master inhibitor of cellular migration and epithelialization in DFUs. Thus, miR193b-3p may represent a target for wound healing induction, cancer therapeutics, and diagnostics.
Abstract IA015: Exploring how competition can be leveraged to improve adaptive therapy in metastatic prostate cancer
Authors: Renee Brady-Nicholls, Heiko Enderling
Journal: Cancer Research (2022)

Abstract Prostate cancer remains the most prevalent cancer in men in the US. While continuous first-line hormone treatment at maximum tolerable dose is the standard of care, continuous treatment often selects for the resistant phenotypes resulting in castration resistant disease. Second-line hormone therapy options, such as abiraterone acetate (AA), have been proven effective for metastatic castration resistant prostate cancer (mCRPC). Adaptive AA, whereby treatment is cycled on and off using patient-specific treatment triggers, has been shown to be effective at reducing toxicity and prolonging time to progression. It is hypothesized that cycling through treatment allows sensitive cells to competitively suppress resistant cells, thereby increasing the amount of time that treatment is effective. It has been proposed that there exists a subset of patients for which this competition can be enhanced through slight modifications to adaptive AA. Here, we investigate this by calibrating a simple mathematical model to longitudinal prostate-specific antigen data from 16 mCRPC patients undergoing adaptive AA. Model parameters are used to simulate modified adaptive therapy and compare against conventional adaptive therapy. Model simulations show that modified adaptive therapy can extend time to progression, while reducing the cumulative dose patients receive. This is a promising first step in improving patient care, particularly in those patients who do not respond well to conventional adaptive therapy. Citation Format: Renee Brady-Nicholls, Heiko Enderling. Exploring how competition can be leveraged to improve adaptive therapy in metastatic prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr IA015.
Defining and assessing intrinsic capacity in older people: A systematic review and a proposed scoring system
Authors: Susana López-Ortiz, Simone Lista, Saúl Peñín-Grandes, Jose Pinto-Fraga, Pedro L. Valenzuela, Robert Nisticò, Enzo Emanuele, Alejandro Lucia, Alejandro Santos-Lozano
Journal: Ageing Research Reviews (2022)